OP0157 EFFECT OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSc-ILD) AND RISK FACTORS FOR RAPID DECLINE IN FORCED VITAL CAPACITY: FURTHER ANALYSES OF THE SENSCIS TRIAL
Authors: D. Khanna, T. Maher, E. Volkmann, Y. Allanore, V. Smith, S. Assassi, M. Kreuter, A. M. Hoffmann-Vold, M. Kuwana, C. Stock, M. Alves, S. Sambevski, C. P. Denton
Journal: Annals of the Rheumatic Diseases (2022)

Background In the SENSCIS trial conducted in a population of subjects with SSc-ILD with a mean time since first non-Raynaud symptom of 3.5 years and 52% with diffuse cutaneous SSc (dcSSc), nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks by 44% versus placebo. Risk factors for a rapid decline in FVC in patients with SSc include early SSc, elevated inflammatory markers, significant skin involvement, and dcSSc. Patients with SSc with these risk factors for rapid progression of ILD are typically given immunosuppressants but not nintedanib. Objectives To analyse the rate of decline in FVC and the effect of nintedanib on FVC decline in subjects with risk factors for a rapid decline in FVC in the SENSCIS trial. Methods In post-hoc analyses of data from the SENSCIS trial, we analysed the rate of decline in FVC (mL/year) over 52 weeks in all subjects and in those with early SSc (&lt;18 months since first non-Raynaud symptom), elevated inflammatory markers (C-reactive protein ≥6 mg/L and/or platelets ≥330 x 10 9 /L), or significant skin fibrosis using two approaches (modified Rodnan skin score [mRSS] 15-40 or mRSS &gt;18) at baseline. We also analysed the rate of decline in FVC over 52 weeks in subjects with one of these risk factors and dcSSc. Results Of 575 subjects analysed, 79 (13.7%) had &lt;18 months since first non-Raynaud symptom, 210 (36.5%) had elevated inflammatory markers, 172 (29.9%) had mRSS 15-40 and 118 (20.5%) had mRSS &gt;18. Of 299 subjects with dcSSc, 29 (9.7%) had &lt;18 months since onset of first non-Raynaud symptom, 129 (43.1%) had elevated inflammatory markers, 162 (54.2%) had mRSS 15-40 and 118 (39.5%) had mRSS &gt;18. In the placebo group, the rate of decline in FVC over 52 weeks was numerically greater in subjects with these risk factors for rapid decline in FVC compared with all subjects (Figure 1). Across the subgroups, the rate of decline in FVC was numerically lower in subjects treated with nintedanib than placebo (Figure 1). Figure 1. Rate of decline in FVC (mL/year) over 52 weeks in (A) all patients and in patients with risk factors for rapid decline in FVC at baseline and (B) all patients and in patients with dcSSc and risk factors for rapid decline in FVC at baseline in the SENSCIS trial. Conclusion The SENSCIS trial included a broad range of subjects with a fibrotic ILD complicating SSc, including those with risk factors for a rapid decline in FVC. In the placebo group, subjects with these risk factors had a more rapid decline in FVC over 52 weeks compared with the overall trial population. By targeting fibrosis with nintedanib, the rate of decline in FVC in patients with risk factors for FVC decline was reduced in patients treated with nintedanib compared with placebo. Acknowledgements The SENSCIS trial was funded by Boehringer Ingelheim. Toby M Maher and Masataka Kuwana were members of the SENSCIS trial Steering Committee. Disclosure of Interests Dinesh Khanna Shareholder of: Stocks - Eicos Sciences, Inc, Consultant of: AbbVie, Acceleron, Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, Genentech/Roche, Gilead, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp &amp; Dohme, Mitsubishi Tanabe Pharma, Prometheus, Sanofi-Aventis, Theraly, United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health, Pfizer, Employee of: Leadership/Equity position – Chief Medical Officer - CiviBioPharma/Eicos Sciences, Inc, Toby Maher Speakers bureau: Boehringer Ingelheim, Galapagos, Genentech, Consultant of: AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, Galecto, GlaxoSmithKline R&amp;D, IQVIA, Pliant, Respivant, Roche, Theravance and Veracyte, Grant/research support from: AstraZeneca, GlaxoSmithKline, Elizabeth Volkmann Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim, Corbus, Forbius, Horizon, Kadmon, Yannick Allanore Consultant of: AbbVie, AstraZeneca, Bayer, Boehringer, Mylan, Janssen, Medsenic, Prometheus, Sanofi, Roche, Grant/research support from: Alpine Immunosciences, Medsenic, OSE Immunotherapeutics, Vanessa Smith Speakers bureau: Actelion Pharmaceuticals, Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV, UCB Biopharma Sprl , Consultant of: Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV , Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV, Research Foundation - Flanders (FWO), Shervin Assassi Speakers bureau: On speaker bureau for Integrity Continuing Education, Consultant of: Abbvie, AstraZeneca, Boehringer Ingelheim, CSL Behring, Novartis, Grant/research support from: Boehringer Ingelheim, Janssen, Michael Kreuter Speakers bureau: Boehringer Ingelheim and Roche, Consultant of: Boehringer Ingelheim and Roche, Grant/research support from: Boehringer Ingelheim and Roche, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Paid instructor for: Boehringer Ingelheim, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Masataka Kuwana Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai, Eisai, GlaxoSmithKline, Janssen, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi , Consultant of: AstraZeneca, Boehringer Ingelheim, Corbus, Kissei, Mochida , Grant/research support from: Boehringer Ingelheim, MBL, Ono Pharmaceuticals , Christian Stock Employee of: Christian Stock is an employee of Boehringer Ingelheim, Margarida Alves Employee of: Margarida Alves is an employee of Boehringer Ingelheim, Steven Sambevski Employee of: Steven Sambevski is an employee of Boehringer Ingelheim, Christopher P Denton Speakers bureau: Boehringer Ingelheim, Janssen, Consultant of: Abbvie, Acceleron, Boehringer Ingelheim, Corbus, CSL Behring, GlaxoSmithKline, Roche, Grant/research support from: ARXX Therapeutics, GlaxoSmithKline, Horizon Therapeutics, Servier